Serum bile acids in patients with hepatopulmonary syndrome.

Background Hepatopulmonary syndrome (HPS) occurs in 20 - 30 % of patients with cirrhosis and is associated with increased mortality. Cholestasis and accumulation of bile acids (BAs) play a major role in chronic liver disease. Aim We aimed to evaluate the clinical role of serum BAs in patients with HPS. Methods Seventy-four patients with cirrhosis were included in this prospective study. Marker for cholestasis as total and individual serum BAs, bilirubin, alkaline phosphatase (AP), and gamma-glutamyl transpeptidase (GGT) were analyzed in patients screened for HPS. Criteria of HPS were fulfilled in 26 patients (35 %). Results In contrast to AP and GGT, bilirubin and serum BAs were significantly elevated in patients with HPS (median total BAs in HPS 83.5 μmol/L, IQR 43.1 - 148.9 vs. no HPS 26.9 μmol/L, 11 - 75.6; p < 0.001). Total BAs correlated with gas exchange by means of PaO2 / AaPO2 (r: -0.28, p < 0.05; r: 0.24, p < 0.05) and portal pressure (r: 0.33, p < 0.05). BAs were associated with HPS independently severity of underlying liver disease (OR: 1.012, 95 % CI: 1.001 - 1.023, p < 0.05). Conclusion BA retention is associated with HPS and gas exchange abnormalities. Future studies should assess whether modulation of BAs signaling may impact the course of HPS.

[1]  M. Trauner,et al.  Serum bile acids as marker for acute decompensation and acute‐on‐chronic liver failure in patients with non‐cholestatic cirrhosis , 2017, Liver international : official journal of the International Association for the Study of the Liver.

[2]  Liguo Wang,et al.  MicroRNA-101 inhibits proliferation of pulmonary microvascular endothelial cells in a rat model of hepatopulmonary syndrome by targeting the JAK2/STAT3 signaling pathway. , 2015, Molecular medicine reports.

[3]  Xiaobo Wang,et al.  MicroRNA-199a-5p Regulates the Proliferation of Pulmonary Microvascular Endothelial Cells in Hepatopulmonary Syndrome , 2015, Cellular Physiology and Biochemistry.

[4]  R. Franchis Expanding consensus in portal hypertension Report of the Baveno VI Consensus Workshop: Stratifying risk and individualizing care for portal hypertension , 2015 .

[5]  Hui-Chun Huang,et al.  Rosuvastatin improves hepatopulmonary syndrome through inhibition of inflammatory angiogenesis of lung. , 2015, Clinical science.

[6]  S. Coulon,et al.  Role of angiogenic factors/cell adhesion markers in serum of cirrhotic patients with hepatopulmonary syndrome , 2015, Liver international : official journal of the International Association for the Study of the Liver.

[7]  J. Chiang,et al.  Bile acids as metabolic regulators , 2015, Current opinion in gastroenterology.

[8]  Sabine Weiskirchen,et al.  Bile Duct Ligation in Mice: Induction of Inflammatory Liver Injury and Fibrosis by Obstructive Cholestasis , 2015, Journal of visualized experiments : JoVE.

[9]  B. Yi,et al.  A comparison of two common bile duct ligation methods to establish hepatopulmonary syndrome animal models , 2015, Laboratory animals.

[10]  M. Trauner,et al.  Von Willebrand factor antigen for detection of hepatopulmonary syndrome in patients with cirrhosis. , 2014, Journal of hepatology.

[11]  F. Lammert,et al.  Bacterial infections in cirrhosis: a position statement based on the EASL Special Conference 2013. , 2014, Journal of hepatology.

[12]  M. Fallon,et al.  Pulmonary complications in chronic liver disease , 2014, Hepatology.

[13]  H. Kumar,et al.  Synthetic FXR agonist GW4064 is a modulator of multiple G protein-coupled receptors. , 2014, Molecular endocrinology.

[14]  E. Hickey,et al.  G Protein–Coupled Bile Acid Receptor 1 Stimulation Mediates Arterial Vasodilation through a KCa1.1 (BKCa)–Dependent Mechanism , 2014, The Journal of Pharmacology and Experimental Therapeutics.

[15]  T. Horvatits,et al.  Therapeutic options in pulmonary hepatic vascular diseases , 2014, Expert review of clinical pharmacology.

[16]  S. Kluge,et al.  Pulmonale Komplikationen bei Lebererkrankungen , 2014, Medizinische Klinik - Intensivmedizin und Notfallmedizin.

[17]  P. Dawson,et al.  Inhibition of ileal apical but not basolateral bile acid transport reduces atherosclerosis in apoE⁻/⁻ mice. , 2013, Atherosclerosis.

[18]  C. Datz,et al.  Austrian consensus on the definition and treatment of portal hypertension and its complications (Billroth II) , 2013, Wiener klinische Wochenschrift.

[19]  M. Trauner,et al.  Hypoxic liver injury and cholestasis in critically ill patients , 2013, Current opinion in critical care.

[20]  M. Fallon,et al.  Pulmonary vascular complications of liver disease. , 2013, American journal of respiratory and critical care medicine.

[21]  M. Trauner,et al.  Bile acid transporters and regulatory nuclear receptors in the liver and beyond , 2013, Journal of hepatology.

[22]  C. Zauner,et al.  Jaundice increases the rate of complications and one‐year mortality in patients with hypoxic hepatitis , 2012, Hepatology.

[23]  Jürgen Popp,et al.  Liver Dysfunction and Phosphatidylinositol-3-Kinase Signalling in Early Sepsis: Experimental Studies in Rodent Models of Peritonitis , 2012, PLoS medicine.

[24]  M. Fallon,et al.  The role of CX₃CL1/CX₃CR1 in pulmonary angiogenesis and intravascular monocyte accumulation in rat experimental hepatopulmonary syndrome. , 2012, Journal of hepatology.

[25]  M. Fallon,et al.  Hepatopulmonary syndrome: update on pathogenesis and clinical features , 2012, Nature Reviews Gastroenterology &Hepatology.

[26]  H. Jaeschke,et al.  Effect of bile duct ligation on bile acid composition in mouse serum and liver , 2012, Liver international : official journal of the International Association for the Study of the Liver.

[27]  J. Raufman,et al.  Bile Acids Regulate Cardiovascular Function , 2011, Clinical and translational science.

[28]  H. Jaeschke,et al.  Bile acids induce inflammatory genes in hepatocytes: a novel mechanism of inflammation during obstructive cholestasis. , 2011, The American journal of pathology.

[29]  O. Briz,et al.  Bile-acid-induced cell injury and protection. , 2009, World journal of gastroenterology.

[30]  Johan Auwerx,et al.  Targeting bile-acid signalling for metabolic diseases , 2008, Nature Reviews Drug Discovery.

[31]  R. Rodríguez-Roisín,et al.  Hepatopulmonary syndrome--a liver-induced lung vascular disorder. , 2008, The New England journal of medicine.

[32]  M. Trauner,et al.  Lessons from the toxic bile concept for the pathogenesis and treatment of cholestatic liver diseases , 2008, Wiener Medizinische Wochenschrift.

[33]  M. Vacca,et al.  Parallel intestinal and liver injury during early cholestasis in the rat: modulation by bile salts and antioxidants. , 2007, Free radical biology & medicine.

[34]  M. Trauner,et al.  Mechanisms of Disease: mechanisms and clinical implications of cholestasis in sepsis , 2006, Nature Clinical Practice Gastroenterology &Hepatology.

[35]  R. Rodríguez-Roisín,et al.  Pulmonary–Hepatic vascular Disorders (PHD) , 2004, European Respiratory Journal.

[36]  M. Humbert,et al.  Prevention of hepatopulmonary syndrome and hyperdynamic state by pentoxifylline in cirrhotic rats , 2004, European Respiratory Journal.

[37]  W. Grizzle,et al.  Increased pulmonary vascular endothelin B receptor expression and responsiveness to endothelin-1 in cirrhotic and portal hypertensive rats: a potential mechanism in experimental hepatopulmonary syndrome. , 2003, Journal of hepatology.

[38]  M. Humbert,et al.  Prevention of gram-negative translocation reduces the severity of hepatopulmonary syndrome. , 2002, American journal of respiratory and critical care medicine.

[39]  N. Javitt Cholesterol, hydroxycholesterols, and bile acids. , 2002, Biochemical and biophysical research communications.

[40]  R. Sokol,et al.  Bile acid‐induced rat hepatocyte apoptosis is inhibited by antioxidants and blockers of the mitochondrial permeability transition , 2001, Hepatology.

[41]  R. Stauber,et al.  Inflammation‐induced cholestasis , 1999, Journal of gastroenterology and hepatology.

[42]  G. Abrams,et al.  Endothelin-1 in the rat bile duct ligation model of hepatopulmonary syndrome: correlation with pulmonary dysfunction. , 1998, Journal of hepatology.

[43]  M. Fallon,et al.  The role of endothelial nitric oxide synthase in the pathogenesis of a rat model of hepatopulmonary syndrome. , 1997, Gastroenterology.

[44]  J. McGrath,et al.  Common bile duct ligation in the rat: a model of intrapulmonary vasodilatation and hepatopulmonary syndrome. , 1997, The American journal of physiology.

[45]  R. Moseley Sepsis-associated cholestasis. , 1997, Gastroenterology.

[46]  G. Hedenborg,et al.  Serum concentrations and excretion of bile acids in cirrhosis. , 1992, Scandinavian journal of clinical and laboratory investigation.

[47]  D. Alvaro,et al.  Bile acid-induced liver toxicity: relation to the hydrophobic-hydrophilic balance of bile acids. , 1986, Medical hypotheses.

[48]  T. Sauerbruch,et al.  Prognostic significance of serum bile acids in cirrhosis , 1986, Hepatology.

[49]  H. Takase,et al.  Effect of bile duct ligation on bile acid metabolism in rats. , 1981, Journal of lipid research.

[50]  G. Neale,et al.  Serum bile acids in liver disease , 1971, Gut.